A 4-substituted-3-halogeno-1,4-benzoxazepine derivative is an important compound usable as a pharmaceutical for psychoneurotic disorders such as anxiety neurosis, phobias, obsessive-compulsive disorders, schizophrenia, post-cardiac trauma stress disorders, depression disorders, and psychosomatic disorders, disorders such as eating disorders, menopausal disorders, infantile autism and also emesis or disorders involving the cerebral circulatory system accompanying cerebral infarction and cerebral hemorrhaging or as a synthetic starting material or an intermediate of pharmaceuticals etc. However, industrial processes for production thereof which have been fully satisfactory in terms of the operability and yield, are not known in the art.
A process for synthesis of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative is disclosed in, for example, International Publication WO96-24594. That is, this process comprises reacting a benzoxazepine derivative with an acid chloride such as phosphorus oxychloride (POCl.sub.3), thionyl chloride (SOCl.sub.2), while adding acid such as hydrochloric acid or a base such as N,N-diethylaniline, if necessary. However, in this process, since a large amount of acid chloride is used, there is the accompanying risk of the generation of hydrochloric acid gas and a sudden rise in temperature and the generation of bumping, etc. in the neutralization reaction for treatment and decomposition of the excessive acid chloride and, therefore, there was the industrial difficulty. Further, in terms of the yield as well, the yield was 30 to 60%--which cannot be necessarily said to be good. Further, there was the problem that the benzoxazepine derivative starting material would remain in the reaction solution in considerable amounts and it was difficult to separate the starting material compound and the target compound.
In this way, no process has been known which has been fully satisfactory for the industrial production of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative. Therefore, a new process for production of a 4-substituted-3-halogeno-1,4-benzoxazepine derivative is necessary to be developed.